The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. INTRODUCTION: To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. METHODS: Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. RESULTS: After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (- 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%), cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. CONCLUSIONS: In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.

Association of physical activity and sedentary time with structural brain networks-The Maastricht Study.

We assessed whether objectively measured low- and high-intensity physical activity (LPA and HPA) and sedentary time (ST) were associated with white matter connectivity, both throughout the whole brain and in brain regions involved in motor function. In the large population-based Maastricht Study (n = 1715, age 59.6 ± 8.1 (mean ± standard deviation) years, and 48% women), the amounts of LPA, HPA, and ST were objectively measured during 7 days by an activPAL accelerometer. In addition, using 3T structural and diffusion MRI, we calculated whole brain node degree and node degree of the basal ganglia and primary motor cortex. Multivariable linear regression analysis was performed, and we report standardized regression coefficients (stß) adjusted for age, sex, education level, wake time, diabetes status, BMI, office systolic blood pressure, antihypertensive medication, total-cholesterol-to-HDL-cholesterol ratio, lipid-modifying medication, alcohol use, smoking status, and history of cardiovascular disease. Lower HPA was associated with lower whole brain node degree after full adjustment (stß [95%CI] = - 0.062 [- 0.101, - 0.013]; p = 0.014), whereas lower LPA (stß [95%CI] = - 0.013 [- 0.061, 0.034]; p = 0.580) and higher ST (stß [95%CI] = - 0.030 [- 0.081, 0.021]; p = 0.250) was not. In addition, lower HPA was associated with lower node degree of the basal ganglia after full adjustment (stß [95%CI] = - 0.070 [- 0.121, - 0.018]; p = 0.009). Objectively measured lower HPA, but not lower LPA and higher ST, was associated with lower whole brain node degree and node degree in specific brain regions highly specialized in motor function. Further research is needed to establish whether more HPA may preserve structural brain connectivity.

Long-term functional outcome of distal radius fractures is associated with early post-fracture bone stiffness of the fracture region: An HR-pQCT exploratory study.

Identifying determinants of long-term functional outcome after a distal radius fracture is challenging. Previously, we reported on the association between early HR-pQCT measurements and clinical outcome 12 weeks after a conservatively treated distal radius fracture. We extended the follow-up and assessed functional outcome after two years in relation to early HR-pQCT derived bone parameters. HR-pQCT scans of the fracture region were performed in 15 postmenopausal women with a distal radius fracture at 1-2 (baseline), 3-4 weeks and 26 months post-fracture. Additionally, the contralateral distal radius was scanned at baseline. Bone density, micro-architecture parameters and bone stiffness using micro-finite element analysis (µFEA) were evaluated. During all visits, wrist pain and function were assessed using the patient-rated wrist evaluation questionnaire (PRWE), quantifying functional outcome with a score between 0 and 100. Two-year PRWE was associated with torsional and bending stiffness 3-4 weeks post-fracture (R2: 0.49, p = 0.006 and R2: 0.54, p = 0.003, respectively). In contrast, early micro-architecture parameters of the fracture region or contralateral bone parameters did not show any association with long-term outcome. This exploratory study indicates that HR-pQCT with µFEA performed within four weeks after a distal radius fracture captures biomechanical fracture characteristics that are associated with long-term functional outcome and therefore could be a valuable early outcome measure in clinical trials and clinical practice.

The association between insulin use and volumetric bone mineral density, bone micro-architecture and bone strength of the distal radius in patients with type 2 diabetes - The Maastricht study.

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62±7.5years, 44% women) was used. Participants were classified as insulin user (n=13) or non-insulin user (n=37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (ß):-0.56 (95% CI:-0.89 to -0.24)), trabecular vBMD (ß:-0.58 (95% CI:-0.87 to -0.30)), trabecular thickness (ß:-0.55 (95% CI:-0.87 to -0.23)), cortical thickness (ß:-0.41 (95% CI:-0.74 to -0.08)), log cortical pore volume (ß:-0.43 (95% CI:-0.73 to -0.13)), bone stiffness (ß:-0.39 (95% CI:-0.62 to -0.17)) and failure load (ß:-0.39 (95% CI:-0.60 to -0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.

Novel radiopaque ultrahigh molecular weight polyethylene sublaminar wires in a growth-guidance system for the treatment of early-onset scoliosis: feasibility in a large animal study.

STUDY DESIGN: In vivo analysis in an ovine model. OBJECTIVE: To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. SUMMARY OF BACKGROUND DATA: Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. METHODS: Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. RESULTS: No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. CONCLUSION: This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. LEVEL OF EVIDENCE: N/A.